Abstract

Acute renal failure caused by Lianbizhi® injection can be attributed to andrographolide sodium bisulphite (ASB) and its main related substance RS413. For the safety evaluation of ASB and RS413, the pharmacokinetics of both compounds in rats was investigated through a liquid chromatography-tandem mass spectrometry method. After a simple protein precipitation with methanol, ASB and RS413 with dehydroandrographolide as an internal standard in plasma were separated on a C₁₈ column using gradient elution with methanol and water and detected in the negative selected reaction monitoring mode. The intra- and inter-day accuracies of the method varied from 96 to 107% over the concentration range of 10–1000 ng/mL. Precisions were within 7.8% and the extraction recoveries ranged between 71–99% without obvious matrix effects. The method was applied for the simultaneous quantification of ASB and RS413 in rats treated intravenously with ASB and RS413 at the dose of 80 mg/kg for the first time.

中文翻译：

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液相色谱-串联质谱法测定穿心莲内酯亚硫酸氢钠及其相关物质的药代动力学

摘要

Lianbizhi®注射引起的急性肾功能衰竭可归因于穿心莲内酯亚硫酸氢钠（ASB）及其主要相关物质RS413。为了评估ASB和RS413的安全性，通过液相色谱-串联质谱法研究了这两种化合物在大鼠中的药代动力学。用甲醇简单沉淀后，将血浆中以脱水穿心莲内酯为内标的ASB和RS413分离在C _18上色谱柱，使用甲醇和水进行梯度洗脱，并以阴性选定的反应监测模式进行检测。在10–1000 ng / mL的浓度范围内，该方法的日内和日间准确性从96％到107％不等。精密度在7.8％以内，萃取回收率在71–99％之间，没有明显的基质影响。该方法用于首次定量以80 mg / kg剂量的ASB和RS413静脉治疗的大鼠中ASB和RS413的同时定量。